Cytotoxic Dimeric Epipolythiodiketopiperazines from the Ascomycetous Fungus Preussia typharum

نویسندگان

  • Lin Du
  • Andrew J. Robles
  • Jarrod B. King
  • Susan L. Mooberry
  • Robert H. Cichewicz
چکیده

Two new dimeric epipolythiodiketopiperazines, preussiadins A (1) and B (2), together with two known diastereomers, leptosins C (6) and A (7), were obtained from the mycelia of a Preussia typharum isolate. The structures of the new compounds were established by spectroscopic methods, and the absolute configurations of 1 and 2 were assigned by chemical transformations and comparisons of quantum chemical ECD and VCD calculations to experimental data. Compound 1 exhibited potent cytotoxic activity in the NCI-60 cell line panel with an average LC50 value of 251 nM. Further studies demonstrated that 1 circumvents P-glycoprotein-mediated drug resistance, yet had no significant antitumor activity in a xenograft UACC-62 melanoma model.

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عنوان ژورنال:

دوره 77  شماره 

صفحات  -

تاریخ انتشار 2014